3- Chloro-4-nitropyridine-1-oxide

Use of some pyridinium oxides in this reaction was also described and the formed azaphenoxathiin /V-oxides can be easily converted to their mother heterocycles (80JHC989, 87JHC211). When 3-chloro-4-nitropyridine 1-oxide (271) was used, small amounts of products of Smiles rearrangement were... 

A full description of work on the Tschitschibabin amination already mentioned has been published 253, piperidine replaces the halogen atom from 3-fluoro- and 3-chloro-4-nitropyridine 1-oxide, whilst with cold sodium methoxide the former gives 3,4-dimethoxypyridine l-oxide 254,... 

Derivatives such as 3-fluoro-4-nitropyridine [13505-01 -6] (396) or the 1-oxide [769-54-0] (397) have been used to characteri2e amino acids and peptides. 5-Eluoro-3-pyridinemethanol [22620-32-2] has been patented as an antihpolytic agent (398). A promising antidepressant, l-(3-fluoro-2-pyridyl)pipera2ine hydrochloride [85386-84-1] is based on 2-chloro-3-fluoropyridine [17282-04-1] (399). 

Chloro-3-nitropyridine [5470-18-8] M 158.5, m 100-103°, 101-102°, 103-104° (sublimes), pK -2.6. Forms needles from H2O. Purified by continuous sublimation over a period of 2 weeks at 50-60°/0.1mm [Barlin J Chem Soc 2150 1964]. The N-oxide has m 99-100°(from CH2Cl2-Et20). [Taylor and Driscoll J Org Chem 25 1716 I960-, Ochiai and Kaneko Chem Pharm Bull Jpn 8 28 I960.]... 

Azathianthrene (382) was prepared in good yield via the corresponding A-oxide 381, obtained by treating 3-chloro-4-nitropyridine-l-oxide (271) with... 

Jawdosiuk et al.220 have treated 4-chloro- and 4-nitropyridine N-oxides (145) with substituted phenylacetonitrile. This is in agreement with the well-known activating effect of N-oxides toward SNAr reactions the results show that nitro is a better leaving group than chloro. 

All these amination reactions show exclusive SNH substitution. There is hardly any indication for the formation of 3-nitropyridines, in which the chloro or methoxy group was replaced by an amino group, even when these leaving groups are present at the reactive a-position of the pyridine ring. It seems to be a characteristic feature of the oxidative amination... 

C7H8N203 2,5-dimethyl-4-nitropyridine-1-oxide 21816-42-2 412.70 35.564 1,2 10940 C7H9CI 5-chloro-5-methyl-1-hexen-3-yne 819-44-3 413.41 35.630 2... 

C7H8N203 3-ethyl-4-nitropyridine-1 -oxide 35363-12-3 463.98 40.434 2 10946 C7H9CIO 3-chloro-2-norbornanone 30860-22-1 373.15 31.843 1,2... 

A useful route for the unequivocal synthesis of complex derivatives of this ring system involves cyclization of compounds of general formula 63. These are readily prepared from the appropriate 2-chloro-3-nitropyridine and an aminoketone. If the requisite amino ketone is too unstable, the corresponding amino alcohol may be used and oxidized to the ketone after reaction with the chloropyridine. 

Very mobile nitro groups can be replaced directly by chlorine or bromine, a reaction that has preparative importance for bromo- and chloro-pyridine and -quinoline derivatives. 5-Ethoxy-2-nitropyridine gives 2-bromo-5-ethoxy-pyridine when heated with HBr in glacial acetic acid in a sealed tube for 3 hours at 130°,1260 and 2-bromo-3-ethoxypyridine is obtained from the corresponding nitro compound and boiling 48% HBr.1261 It is particularly easy to introduce Cl or Br in place of a 4-nitro group in pyridine 1-oxide or quino-... 

Thermolysis of iV-oxides of type (64) yields pyridyl ethers (65) on cleavage with hydrazine, these give a catechol (67) and 2-hydrazino-5-nitropyridine (66). In addition to the ort/io-substituted phenol (65), thermolysis (if R = H) also gives a small amount of para-substituted product. Since the starting materials can be prepared from the reaction of 2-chloro-5-nitropyridine and a phenol, followed by N-oxidation, this represents overall a four-stage process by which a phenol can be converted into a catechol (Scheme 27). ... 

Scheme 48. Improved synthesis of 2-chloro-3-methoxy-4-nitropyridine N-oxide 310).

Preparation of the 2-chloro-3-methoxy-4-nitropyridine A -oxide intermediate in the synthesis was considerably improved by the methylation of commercially available 2-chloro-3-pyridinol using dimethylsulfate and tet-rabutylammonium bromide as the catalyst under phase-transfer conditions (370), instead of diazomethane (Scheme 48). In the synthesis of orellanines elaborated by Tiecco et al. (299,301,309), shown in Scheme 49, the commercially available 3-hydroxypyridine was the starting material. The structures of the synthetic compounds were proved to be identical to those... 

The synthesis of fluoroalkyl-substituted heterocycles is a subject of continuous interest this challenging issue has been presented in details in reviews [107,108]. It has been shown that trifluoromethyl carbanion, generated from (trifluoromethyl) trimethylsilane (the Ruppert reagent), adds easily to 2-chloro-3-nitropyridine. The produced o adducts can be oxidized with dimethyldioxirane (DMD) to form two isomeric 2-chloro-4-(and 6-)trifluoromethyl-3-hydroxypyridines (Scheme 30) [109]. 

Oxidative nucleophilic substitution of hydrogen in 2-chloro-3-nitropyridine by action of iV-Uthio-S, S -diphenylsulfilimines has been shown to be accompanied with the SnAt displacement of chloro atom (Scheme 55). Both of these products were oxidized with m-CPBA to form dinitropyridines [164, 165],... 

The A -oxide function is retained on treatment with nitric and sulfuric acids at somewhat lower temperatures. Thus Talik and Talik prepared 3-chloro-4-nitro-pyridine-1-oxide (84.5%) and 3-iodo-4-nitropyridine-l-oxide (56.4%) with this reagent at steam-bath temperature. 

Talik studied the behavior of 3-chloro-4-nitropyridine-l-oxide with various reagents, and showed that sodium methoxide causes replacement of the nitro group, while amines, on the other hand, effect displacement of the halogen. 

Halo-4-nitropyridine-l-oxides react with two equivalents of sodium methoxide at room temperature to effect replacement of both halogen and nitro groups. One equivalent of sodium methoxide at that temperature, however, causes replacement of the nitro group alone to give 2-chloro-4-methoxypyridine--1-oxide in 84% yield. The use of two equivalents of the base in boiling methanol gives 2,4-dimethoxypyridine-l-oxide. 

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